The biosynthesis, structure and function of the polypeptide chains which comprise the subunits of the keratin filaments of normal human, murine and bovine epidermis are being investigated. The subunits polymerize in vitro into native-type filaments. The details of filament ultrastructure are being investigated using image analysis procedures of filaments examined by transmission electron microscopic and scanning transmission electron microscopic techniques. Model structures generated from these methods will be computationally tested for compatibility with other physico-chemical data and amino acid sequence studies of individual filament subunits. cDNA cloned probes that encode human and mouse epidermal keratins have been isolated and are being used to determine the amino acid sequences of the proteins, and to study the structure and expression of keratin genes. The 10nm filaments of fibroblasts, muscle cells and neuronal tissues have been shown to be structurally similar to, but immunologically different from keratin filaments. A histidine-rich basic protein isolated from human epidermis and the slightly different protein of mouse epidermis specifically aggregate keratin filaments and other 10nm filaments in a manner suggestive of an interfilamentous matrix component. cDNA cloned probes will be isolated to study their structure, expression and amino acid sequence.